An experimental HIV vaccine candidate has delivered encouraging results in a preclinical study involving primates, offering fresh hope in the long-standing effort to prevent HIV infection. Developed by scientists from the La Jolla Institute for Immunology (LJI), Scripps Research and the International AIDS Vaccine Initiative (IAVI), the vaccine is designed to stimulate the production of rare broadly neutralising antibodies capable of combating HIV despite its rapid mutations. According to LJI, it is the first HIV vaccine candidate to generate high levels of these virus-fighting antibodies in primates.
“This feels like a huge success,” said Shane Crotty, chief scientific officer at LJI, who co-led the research with Scripps Research professor William Schief. “We constructed a successful vaccine from the ground up, which required a deep understanding of the immune system.”
The vaccine works by guiding the maturation of B cells, the immune cells responsible for producing antibodies. B cells begin in a naïve state and mature after recognising parts of a pathogen, enabling them to generate antibodies that bind to the pathogen and help prevent infection. As they mature, B cells refine these antibodies to improve their ability to target vulnerable sites on viruses.
Overcoming HIV's complex defence mechanisms
Scientists said HIV has remained a formidable challenge because it employs multiple strategies to evade the immune system. The virus surrounds itself with constantly shifting sugar molecules, known as glycans, allowing it to escape detection by immune cells. It also mutates at an extraordinary rate and changes its shape while infecting human cells, making previously produced antibodies ineffective.
“The worldwide diversity of HIV mutations is extraordinary. Even the diversity within one individual person living with HIV is dramatic,” said Patrick Madden, an LJI instructor who served as study co-first author along with Jon Steichen, an investigator at Scripps Research.
Researchers said these characteristics rarely allow B cells enough time to develop potent broadly neutralising antibodies. To overcome this challenge, the team traced the development of HIV-targeting B cells in reverse to understand how they evolved after exposure to specific parts of the virus. They found that early exposure to portions of HIV's outer envelope protein prompted the development of broadly neutralising antibodies. These viral antigens became the foundation for designing the vaccine molecules.
Promising preclinical results after 14 years of research
The vaccine candidate, developed by the Schief laboratory to closely resemble key HIV antigens, was tested in rhesus macaques at the Emory National Primate Research Center. Researchers found that about 44% of the animals produced broadly neutralising antibodies against HIV, with the antibodies present in substantial quantities.
The findings, published in Nature, are the result of 14 years of collaboration between the La Jolla Institute for Immunology and Scripps Research under the Scripps Consortium for HIV/AIDS Vaccine Development (CHAVD).
“This has been one of those Apollo moon mission-type projects, where there is an exceptional goal and the team has to accomplish a myriad of discoveries and inventions along the way,” Crotty said.
